An interventional study of oral EGF816 in adult patients with EGFRmut solid malignancies

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 500

Inclusion Criteria

1. Written informed consent obtained prior to any screening procedures
2. Patient (male or female) = 18 years of age
3. Patients must have histologically or cytologically confirmed locally
advanced (stage IIIB not amendable to definitive multi-modality therapy
including surgery) or metastatic (stage IV) EGFR mutant NSCLC
4. Patients with controlled brain metastases may participate in the trial.
They must complete any planned radiation therapy and/or surgery > 2
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weeks prior to the first dose of study treatment and remain
asymptomatic. Patients on steroids must have been on a stable low dose
for 2 weeks prior to initiating study treatment.
5. ECOG performance status: Phase I part: 0, 1, or 2; Phase II part: 0 or
1
6. Presence of at least one measurable lesion according to RECIST 1.1
per Investigator assessment. A previously irradiated site lesion may be
counted as a target lesion only if there is clear sign of progression since
the irradiation (see Section 14.1 Appendix 1)
7. Willingness and ability to comply with scheduled visits, treatment
plans, laboratory tests and other study procedures
8. Requirement of EGFR mutation status and prior lines of treatment for
Phase I patients:
• All patients participating in the Phase I part must have recurring or
progressive disease following standard therapy.
• Locally advanced or metastatic NSCLC harboring a documented EGFR
T790M mutation. An archival or newly obtained tumor sample must be
available for molecular pre-screening if prior documentation of EGFR
T790M mutation status is not available; No more than a total of 3 prior
lines of antineoplastic therapies, including EGFR TKI, in the advanced
setting; No prior treatment with any investigational EGFR-TKI targeting
EGFR T790M mutation (i.e. 3rd-generation EGFR TKI)
9. Requirements of EGFR mutation status and prior lines of treatment for
Phase II patients:
• Group 1: Locally advanced or metastatic NSCLC with EGFR activating
mutation (e.g. L858R and/or ex19del); Who have not received any
systemic antineoplastic therapy, including EGFR TKI treatment, for
advanced NSCLC; Note: patients who have received no more than 1 cycle
of chemotherapy in the advanced setting are allowed.
• Group 2: Locally advanced or metastatic NSCLC with EGFR activating
mutation (e.g. L858R and/or ex19del) and an acquired EGFR T790M
mutation; Who have progressed on 1 and only 1 prior treatment with a
1st-generation EGFR TKI (e.g., erlotinib, gefitinib or icotinib) or 2ndgeneration
EGFR TKI (e.g., afatinib or dacomitinib); No more than 3 prior
lines of systemic antineoplastic therapies (including EGFR TKI) in the
advanced setting; 1st/2nd-generation EGFR TKI treatment must be the
last prior treatment before study entry
• Group 3: Locally advanced or metastatic NSCLC with a de novo EGFR
T790M mutation; For purposes of this protocol, de novo T790M will be
defined as the presence of EGFR T790M mutation in NSCLC patients who
have NOT been previously treated with any therapy known to inhibit
EGFR; No more than 3 prior lines of systemic antineoplastic therapies in
the advanced setting; No prior treatment with any therapy known to
inhibit EGFR, including EGFR TKI
• Group 4: Locally advanced or metastatic NSCLC whose tumor harbors
EGFR exon 20 insertion or deletion; No more than 3 prior lines of
systemic antineoplastic therapies, including EGFR TKI, in the advanced
setting
• Group 5: Locally advanced or metastatic

Exclusion Criteria

English For all patients (unless otherwise specified):
1. Patients with a history or presence of interstitial lung disease or
interstitial pneumonitis, including clinically significant radiation
pneumonitis (i.e. affecting activities of daily living or requiring
therapeutic intervention)
2. Patients with tumors harboring an EGFR exon 20 insertion or deletion
(except for Group 4 patients in the Phase II par)
3. Patients with unstable brain metastases.
4. Any medical condition that would, in the investigator's judgment,
prevent the patient's participation in the clinical study due to safety
concerns or compliance with clinical study procedures
5. Patients with out of range laboratory values defined as:
• Absolute Neutrophil Count (ANC) < 1.5 x 10^9/L
• Hemoglobin (Hgb) < 9 g/dL
• Platelets < 75 x 10^9/L
• Total bilirubin >1.5 x ULN. For patients with Gilbert's syndrome total
bilirubin >3.0 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and/or alanine aminotransferase
(ALT) >3 x ULN for patients without hepatic metastasis. AST and/or ALT
>5 x ULN for patients with hepatic metastasis
• Alkaline phosphatase (ALP) > 5 xULN
• Fasting plasma glucose > 175 mg/dL (> 9.8 mmol/L)
• Measured or calculated creatinine clearance < 45 mL/min
6. Patients with electrolytes outside the laboratory normal limits that
cannot be corrected with supplements during screening:
• Potassium
• Magnesium
• Phosphorus
• Total calcium (corrected for serum albumin)
7. Patients receiving treatment with medications that are known to be
strong inhibitors or inducers of CYP3A4/5 and cannot be discontinued 1
week prior to the start of EGF816 treatment and for the duration of the
study.
Other protocol-defined exclusion criteria may apply

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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